Jiang Tao, Mao Houping, Chen Qin, Cao Linsheng, He Yanfeng, Gao Xingjian, Chen Wenwei, Zhang Hua
Department of Urology, Second District, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian Province, China.
Open Med (Wars). 2020 Nov 14;15(1):1153-1162. doi: 10.1515/med-2020-0206. eCollection 2020.
Renal cell carcinoma (RCC) is a malignant tumor originating from renal tubular epithelial cells with poor prognosis and high metastatic rate. Tripartite motif-containing 24 (Trim24) is a member of the tripartite motif (Trim) family and also a valuable oncogene, but its role in RCC remains unclear. We constructed the overexpression and knockdown of Trim24 cell lines to investigate its roles in RCC progression. CCK8, wound healing, and transwell assay were performed to determine the proliferation, migration, and invasion of RCC cell lines, respectively. Moreover, the expression of Trim24 and its clinicopathological significance were evaluated in a human RCC tissue microarray. From our results, Trim24 promoted the proliferation, migration, and invasion of RCC cells . Importantly, overexpression of Trim24 led to a significant increase in the expression levels of MMP-2, MMP-9, fibronectin, snail, vimentin, N-cadherin, and β-catenin, inducing the EMT process in turn, while the expression of these proteins was significantly downregulated when Trim24 was knocked down in ACHN cells. In addition, Trim24 was significantly upregulated in RCC, and its high expression was negatively associated with the tumor size. Trim24 might operate as an oncogene in RCC progression by inducing the EMT process, suggesting that Trim24 was a potential target for human RCC.
肾细胞癌（RCC）是一种起源于肾小管上皮细胞的恶性肿瘤，预后较差且转移率高。含三联基序的蛋白24（Trim24）是三联基序（Trim）家族的成员，也是一种重要的癌基因，但其在肾细胞癌中的作用仍不清楚。我们构建了Trim24过表达和敲低的细胞系，以研究其在肾细胞癌进展中的作用。分别进行CCK8、伤口愈合和Transwell实验，以确定肾细胞癌细胞系的增殖、迁移和侵袭能力。此外，在人肾细胞癌组织芯片中评估了Trim24的表达及其临床病理意义。根据我们的结果，Trim24促进了肾细胞癌细胞的增殖、迁移和侵袭。重要的是，Trim24的过表达导致基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）、纤连蛋白、蜗牛蛋白、波形蛋白、N-钙黏蛋白和β-连环蛋白的表达水平显著增加，进而诱导上皮-间质转化（EMT）过程，而在ACHN细胞中敲低Trim24时，这些蛋白的表达显著下调。此外，Trim24在肾细胞癌中显著上调，其高表达与肿瘤大小呈负相关。Trim24可能通过诱导EMT过程在肾细胞癌进展中发挥癌基因作用，提示Trim24是人类肾细胞癌的一个潜在靶点。
